One of the major techniques for determining the prognosis of cancer, particularly breast cancer, involves examining the lymph nodes of the axilla or armpit of the patient. It is well known that a major aspect in assessing the stage of the cancer revolves around whether the cancer has spread to the lymph nodes. It is therefore important to have an effective technique for identifying the spread of the cancer through the lymphatic system.
In the lymphatic system of the human body, lymphatic fluid flows from the breast through the lymph channels and is filtered through the lymph nodes. The first stop is the “first lymph node” or the “sentinel lymph node.” If the cancer has spread to the lymph nodes, the sentinel lymph node should be positive (i.e., cancerous). If the first lymph node is negative, it can be assumed that the rest of the lymph nodes are negative. Therefore, it is crucial that this first lymph node or sentinel lymph node be accurately identified.
A known technique for identifying the sentinel lymph node(s) involves the use of two substances: a blue dye and a radioactive substance. The blue dye visually stains the sentinel node(s) and the radioactive substance enables the site of the sentinel node(s) to be remotely detected. The blue dye conventionally used for sentinel lymph node procedure is lymphazurine blue, although smaller amounts of methylene blue have also sometimes been used, and still further substances have been suggested. The radioactive substance is a sulfur colloid. These substances are injected separately in or near the tumor or tumor site and flow along the lymphatic system to the sentinel node draining that site. The node can then be located by using a diagnostic device to detect the emissions from the radioactive substance and then visually accessing the node based on staining from the dye.
In less than 10 years from the first reports utilizing this technique, literally hundreds of studies have appeared in the scientific literature validating the use of sentinel node biopsy as an accurate method to evaluate the risk of harboring metastatic disease in axillary nodes. Almost simultaneously, reports appeared in the literature documenting the success of sentinel node localization using lymphazurin blue dye with or without technetium 99 labeled sulfur colloid. However, following the publication of large studies from Louisville as well as Memorial Sloan-Kettering, documenting improved success at harvesting the sentinel node as well as comparable accuracy, the majority of breast surgeons prefer to use both dye and radiocolloid for their evaluation of sentinel nodes.
Recently several reports have appeared suggesting that sentinel node accuracy and yield could be duplicated with the use of methylene blue dye as opposed to the lymphazurin blue dye. This change in dye preference has also found its way into practice of many surgeons. Injection of small quantities (0.1-0.5 cc) of methylene blue has been used for years. These small quantities of methylene blue are injected into the breast following wire-localization procedures and are associated with no reported adverse events.
With the development of sentinel node biopsy came some unanticipated consequences for both surgeon and patient alike. Patients must undergo a separate procedure for injecting the radiocolloid prior to their cancer surgery. This part of the procedure is carried out either the afternoon prior to surgery or the morning of surgery, usually within a couple of hours of the surgical procedure. The injection of radiocolloid is unusually painful whether it is injected in small quantities intradermally or in larger quantities around the tumor. With the increasing demand for sentinel lymph node sampling surgeons have been forced to deal with major delays in their surgical schedules because of the necessity of an additional preoperative procedure that is at the direction of non-operating room personnel.
Other shortcomings of the known procedures include the fact that 99M Tc sulfur colloid has high-energy gamma emissions and a significant amount of activity (10 mCi) has to be initially injected to ensure adequate node uptake. Some of the activity must clear from the injection site before use of the hand held gamma probe in the axilla. Failure to allow clearance of the radiolabeled colloid “swamps” the gamma detector making identification of the sentinel node impossible or at least much more difficult.
Therefore, there is a need for a composition that enables an improved and simplified technique for the identification of the sentinel lymph node.